Nanosecond-Scale Proton Emission from Strongly Oblate-Deformed

Using the fusion-evaporation reaction ^{96}Ru(^{58}Ni,p4n)^{149}Lu and the MARA vacuum-mode recoil separator, a new proton-emitting isotope ^{149}Lu has been identified. The measured decay Q value of 1920(20) keV is the highest measured for a ground-state proton decay, and it naturally leads to the shortest directly measured half-life of 450_{-100}^{+170} ns for a ground-state proton emitter. The decay rate is consistent with l_{p}=5 emission, suggesting a dominant πh_{11/2} component for the wave function of the proton-emitting state. Through nonadiabatic quasiparticle calculations it was concluded that ^{149}Lu is the most oblate deformed proton emitter observed to date.

Evolutionary and structural analyses uncover a role for solvent interactions in the diversification of cocoonases in butterflies.

Multi-omic approaches promise to supply the power to detect genes underlying disease and fitness-related phenotypes. Optimal use of the resulting profusion of data requires detailed investigation of individual candidate genes, a challenging proposition. Here, we combine transcriptomic and genomic data with molecular modelling of candidate enzymes to characterize the evolutionary history and function of the serine protease cocoonase. Heliconius butterflies possess the unique ability to feed on pollen; recent work has identified cocoonase as a candidate gene in pollen digestion. Cocoonase was first described in moths, where it aids in eclosure from the cocoon and is present as a single copy gene. In heliconiine butterflies it is duplicated and highly expressed in the mouthparts of adults. At least six copies of cocoonase are present in Heliconius melpomene and copy number varies across H. melpomene sub-populations. Most cocoonase genes are under purifying selection, however branch-site analyses suggest cocoonase 3 genes may have evolved under episodic diversifying selection. Molecular modelling of cocoonase proteins and examination of their predicted structures revealed that the active site region of each type has a similar structure to trypsin, with the same predicted substrate specificity across types. Variation among heliconiine cocoonases instead lies in the outward-facing residues involved in solvent interaction. Thus, the neofunctionalization of cocoonase duplicates appears to have resulted from the need for these serine proteases to operate in diverse biochemical environments. We suggest that cocoonase may have played a buffering role in feeding during the diversification of Heliconius across the neotropics by enabling these butterflies to digest protein from a range of biochemical milieux.

Curious bivalves: Systematic utility and unusual properties of anomalodesmatan mitochondrial genomes.

Mitogenomic trees for Bivalvia have proved problematic in the past, but several highly divergent lineages were missing from these analyses and increased representation of these groups may yet improve resolution. Here, we add seven new sequences from the Anomalodesmata and one unidentified semelid species (Bryopa lata, Euciroa cf. queenslandica, Laternula elliptica, Laternula truncata, Lyonsia norwegica, Myadora brevis, Tropidomya abbreviata, "Abra" sp.). We show that relationships in a mitogenomic tree for the Class are improved by the addition of seven anomalodesmatans from this highly divergent clade, but are still not completely consistent with relationships recovered in studies of nuclear genes. We suggest that some anomalous relationships (for instance the non-monophyly of Bivalvia) may be partially explained by compositional heterogeneity in the mitogenome and suggest that the addition of more taxa may help resolve both this effect and possible instances of long branch attraction. We also identify several curious features about anomalodesmatan mitogenomes. For example, many protein-coding gene boundaries are poorly defined in marine bivalves, but particularly so in anomalodesmatans, primarily due to non-conserved boundary sequences. The use of transcriptomic and genomic data together enabled better definition of gene boundaries, the identification of possible pseudogenes and suggests that most genes are translated monocistronically, which contrasts with many other studies. We also identified a possible case of gene duplication of ND5 in Myadora brevis (Myochamidae). Mitogenome size in the Anomalodesmata ranges from very small compact molecules, with the smallest for Laternula elliptica (Laternulidae) only 14,622bp, to Bryopa lata (Clavagellidae) which is at least 31,969bp long and may be >40,000bp. Finally, sampled species show a high degree of sequence divergence and variable gene order, although intraspecific variation in Laternula elliptica is very low.

A comparison of polymer and polymer-hydroxyapatite composite tissue engineered scaffolds for use in bone regeneration. An in vitro and in vivo study.

Previous in vitro work demonstrated porous PLA and PLGA both had the mechanical strength and sustained the excellent skeletal stem cell (SSC) growth required of an osteogenic bonegraft substitute, for use in impaction bone grafting. The purpose of this investigation was to assess the effects of the addition of hydroxyapatite (HA) to the scaffolds before clinical translation. PLA, PLA+10% HA, PLGA, and PLGA+10% HA were milled and impacted into discs before undergoing a standardized shear test. Cellular compatibility analysis followed 14 days incubation with human skeletal stems cells (SSC). The best two performing polymers were taken forward for in vivo analysis. SSC seeded polymer discs were implanted subcutaneously in mice. All polymers had superior mechanical shear strength compared with allograft (p < 0.01). Excellent SSC survival was demonstrated on all polymers, but the PLA polymers showed enhanced osteoblastic activity (ALP assay p < 0.01) and collagen-1 formation. In vivo analysis was performed on PLA and PLA+10% HA. MicroCT analysis revealed increased bone formation on the PLA HA (p < 0.01), and excellent neo-vessel formation in both samples. Histology confirmed evidence of de novo bone formation. PLA HA showed both enhanced osteoinductive and osteogenic capacity. This polymer composite has been selected for scaled-up experimentation before clinical translation.

From bench to clinic and back: skeletal stem cells and impaction bone grafting for regeneration of bone defects.

Tissue engineering offers enormous potential for bone regeneration. Despite extensive in vitro and in vivo work, few strategies translate into clinical practice. This paper describes the combination of skeletal stem cells (SSCs) and impaction bone grafting (IBG) for the treatment of patients with bone defects associated with avascular necrosis of the femoral head. SSCs and milled allograft were impacted into necrotic bone in the femoral heads of four patients. Three patients remained asymptomatic at 22-44 month follow-up, but one patient has required total hip replacement (both hips). This has allowed retrieval of the femoral heads, which were analysed structurally and functionally by µCT, histology and mechanical testing. A central channel of impacted bone was found in the femoral heads, which displayed a mature trabecular micro-architecture. The impacted bone was denser than the surrounding trabecular bone, as strong in compression and with histological micro-architecture comparable to that of trabecular bone. Analysis of the retrieved femoral head samples has demonstrated that this tissue-engineering strategy regenerates bone that is both structurally and functionally analogous to normal trabecular bone. SSCs, together with IBG, have proved an effective treatment for avascular necrosis of the femoral head and offer significant potential for the broader spectrum of bone defects.

A tissue engineering strategy for the treatment of avascular necrosis of the femoral head.

BACKGROUND & PURPOSE: Skeletal stem cells (SSCs) and impaction bone grafting (IBG) can be combined to produce a mechanically stable living bone composite. This novel strategy has been translated to the treatment of avascular necrosis of the femoral head. Surgical technique, clinical follow-up and retrieval analysis data of this translational case series is presented. METHODS: SSCs and milled allograft were impacted into necrotic bone in five femoral heads of four patients. Cell viability was confirmed by parallel in vitro culture of the cell-graft constructs. Patient follow-up was by serial clinical and radiological examination. Tissue engineered bone was retrieved from two retrieved femoral heads and was analysed by histology, microcomputed tomography (µCT) and mechanical testing. RESULTS: Three patients remain asymptomatic at 22- to 44-month follow-up. One patient (both hips) required total hip replacement due to widespread residual necrosis. Retrieved tissue engineered bone demonstrated a mature trabecular micro-architecture histologically and on µCT. Bone density and axial compression strength were comparable to trabecular bone. CONCLUSIONS: Clinical follow-up shows this to be an effective new treatment for focal early stage avascular necrosis of the femoral head. Unique retrieval analysis of clinically translated tissue engineered bone has demonstrated regeneration of tissue that is both structurally and functionally analogous to normal trabecular bone.

Supercritical CO2 fluid-foaming of polymers to increase porosity: a method to improve the mechanical and biocompatibility characteristics for use as a potential alternative to allografts in impaction bone grafting?

Disease transmission, availability and cost of allografts have resulted in significant efforts to find an alternative for use in impaction bone grafting (IBG). Recent studies identified two polymers with both structural strength and biocompatibility characteristics as potential replacements. The aim of this study was to assess whether increasing the polymer porosity further enhanced the mechanical and cellular compatibility characteristics for use as an osteogenic biomaterial alternative to allografts in IBG. Solid and porous poly(DL-lactide) (P(DL)LA) and poly(DL-lactide-co-glycolide) (P(DL)LGA) scaffolds were produced via melt processing and supercritical CO(2) foaming, and the differences characterized using scanning electron microscopy (SEM). Mechanical testing included milling and impaction, with comparisons made using a shear testing rig as well as a novel agitation test for cohesion. Cellular compatibility tests for cell number, viability, and osteogenic differentiation using WST-1 assays, fluorostaining, and ALP assays were determined following 14 day culture with skeletal stem cells. SEM showed excellent porosity throughout both of the supercritical-foam-produced polymer scaffolds, with pores between 50 and 200 µm. Shear testing showed that the porous polymers exceeded the shear strength of allograft controls (P<0.001). Agitation testing showed greater cohesion between the particles of the porous polymers (P<0.05). Cellular studies showed increased cell number, viability, and osteogenic differentiation on the porous polymers compared to solid block polymers (P<0.05). The use of supercritical CO(2) to generate porous polymeric biodegradable scaffolds significantly improves the cellular compatibility and cohesion observed compared to non-porous counterparts, without substantial loss of mechanical shear strength. These improved characteristics are critical for clinical translation as a potential osteogenic composite for use in IBG.

Polymerisation stress modelling in acrylic bone cement.

Fatigue failure of the cement mantle has been proposed as one of the failure processes contributing to aseptic loosening of cemented joint replacements. It has also been suggested that fatigue failure is dramatically accelerated by residual stress generated during the cement polymerisation process. Previous computational models of the polymerisation process have investigated only the latter part of polymerisation by assuming both instantaneous hardening of the material (a stress locking point) and that all residual stress results from thermal shrinkage after this stress locking point. In this study, finite element models which use the local degree of polymerisation to calculate material properties and shrinkage have been used to predict residual stresses in two models of total hip replacement cement mantles. Results indicate that the final value of cement mantle stress may not be the highest stresses that the cement is subjected to during the polymerisation process. Two models are presented, a 2-dimensional model, which was adapted from a similar model in the literature (Lennon and Prendergast, 2002) and a 3-dimensional concentric-cylinders model. In both cases a chemical kinetics model was used to predict the progress of the polymerisation reaction and a second linear model used to predict cement mechanical properties and density, and so stress generation and volume change, over time. There was good agreement of the results of the 2D model with its counterpart in the literature. For the 3D model, the final residual stress magnitudes and patterns showed good agreement with similar physical and computational models in the literature.

Cementing techniques in hip resurfacing.

The subject of the cementing technique in hip resurfacing has been poorly studied to date. The hip resurfacing prosthesis is unique in the family of cemented prostheses because the cement mantle is blind (hidden underneath the implant) and is radiographically obscured. This presents an immediate challenge to the surgeon at the time of surgery, but also has a longer-term implication in terms of lack of post-operative clinical observation. This should be compared with total hip replacement or total knee replacement where the cement mantle can at least be partially observed both intra- and post-operatively. With this in mind, the objective of this review is, firstly, to understand the cement mantles typically achieved in current clinical practice and, secondly, to identify those factors affecting the cement mantle and to consolidate them into an improved and reproducible cementing technique. The outcome of this work shows that the low-viscosity technique can commonly lead to excessive cement penetration in the proximal femoral head and an incompletely seated component, whereas a more consistent controlled cement mantle can be achieved with a high-viscosity cementing technique. Consequently, it is recommended that a high-viscosity technique should be used to minimize the build-up of excessive cement, to reduce the temperature created by the exothermic polymerization, and to help to ensure correct seating of the prosthesis. A combination of these factors is potentially critical to the clinical success of some articular surface replacement (ASR) procedures. It is important to note that we specifically studied the DePuy ASR system; therefore only the general principles (and not the specifics) of the cementing technique may apply to other resurfacing prostheses, because of differences in internal geometry, clearance, and surgical technique.

Functional diversification of lepidopteran opsins following gene duplication.

A comparative approach was taken for identifying amino acid substitutions that may be under positive Darwinian selection and are correlated with spectral shifts among orthologous and paralogous lepidopteran long wavelength-sensitive (LW) opsins. Four novel LW opsin fragments were isolated, cloned, and sequenced from eye-specific cDNAs from two butterflies, Vanessa cardui (Nymphalidae) and Precis coenia (Nymphalidae), and two moths, Spodoptera exigua (Noctuidae) and Galleria mellonella (Pyralidae). These opsins were sampled because they encode visual pigments having a naturally occurring range of lambda(max) values (510-530 nm), which in combination with previously characterized lepidopteran opsins, provide a complete range of known spectral sensitivities (510-575 nm) among lepidopteran LW opsins. Two recent opsin gene duplication events were found within the papilionid but not within the nymphalid butterfly families through neighbor-joining, maximum parsimony, and maximum likelihood phylogenetic analyses of 13 lepidopteran opsin sequences. An elevated rate of evolution was detected in the red-shifted Papilio Rh3 branch following gene duplication, because of an increase in the amino acid substitution rate in the transmembrane domain of the protein, a region that forms the chromophore-binding pocket of the visual pigment. A maximum likelihood approach was used to estimate omega, the ratio of nonsynonymous to synonymous substitutions per site. Branch-specific tests of selection (free-ratio) identified one branch with omega = 2.1044, but the small number of substitutions involved was not significantly different from the expected number of changes under the neutral expectation of omega = 1. Ancestral sequences were reconstructed with a high degree of certainty from these data. Reconstructed ancestral sequences revealed several instances of convergence to the same amino acid between butterfly and vertebrate cone pigments, and between independent branches of the butterfly opsin tree that are correlated with spectral shifts.

The teflon gene is required for maintenance of autosomal homolog pairing at meiosis I in male Drosophila melanogaster.

In recombination-proficient organisms, chiasmata appear to mediate associations between homologs at metaphase of meiosis I. It is less clear how homolog associations are maintained in organisms that lack recombination, such as male Drosophila. In lieu of chiasmata and synaptonemal complexes, there must be molecules that balance poleward forces exerted across homologous centromeres. Here we describe the genetic and cytological characterization of four EMS-induced mutations in teflon (tef), a gene involved in this process in Drosophila melanogaster. All four alleles are male specific and cause meiosis I-specific nondisjunction of the autosomes. They do not measurably perturb sex chromosome segregation, suggesting that there are differences in the genetic control of autosome and sex chromosome segregation in males. Meiotic transmission of univalent chromosomes is unaffected in tef mutants, implicating the tef product in a pairing-dependent process. The segregation of translocations between sex chromosomes and autosomes is altered in tef mutants in a manner that supports this hypothesis. Consistent with these genetic observations, cytological examination of meiotic chromosomes suggests a role of tef in regulating or mediating pairing of autosomal bivalents at meiosis I. We discuss implications of this finding in regard to the evolution of heteromorphic sex chromosomes and the mechanisms that ensure chromosome disjunction in the absence of recombination.

The evolution of color vision in insects.

We review the physiological, molecular, and neural mechanisms of insect color vision. Phylogenetic and molecular analyses reveal that the basic bauplan, UV-blue-green-trichromacy, appears to date back to the Devonian ancestor of all pterygote insects. There are variations on this theme, however. These concern the number of color receptor types, their differential expression across the retina, and their fine tuning along the wavelength scale. In a few cases (but not in many others), these differences can be linked to visual ecology. Other insects have virtually identical sets of color receptors despite strong differences in lifestyle. Instead of the adaptionism that has dominated visual ecology in the past, we propose that chance evolutionary processes, history, and constraints should be considered. In addition to phylogenetic analyses designed to explore these factors, we suggest quantifying variance between individuals and populations and using fitness measurements to test the adaptive value of traits identified in insect color vision systems.

Six opsins from the butterfly Papilio glaucus: molecular phylogenetic evidence for paralogous origins of red-sensitive visual pigments in insects.

It has been hypothesized that the UV-, blue-, and green-sensitive visual pigments of insects were present in the common ancestor of crustaceans and insects, whereas red-sensitive visual pigments evolved later as a result of convergent evolution. This hypothesis is examined with respect to the placement of six opsins from the swallowtail butterfly Papilio glaucus (PglRh1-6) in relationship to 46 other insect, crustacean, and chelicerate opsin sequences. All basal relationships established with maximum parsimony analysis except two are present in the distance and maximum likelihood analyses. In all analyses, the six P. glaucus opsins fall into three well-supported clades, comprised, respectively, of ultraviolet (UV), blue, and long-wavelength (LW) pigments, which appear to predate the radiation of the insects. Lepidopteran green- and red-sensitive visual pigments form a monophyletic clade, which lends support to the hypothesis from comparative physiological studies that red-sensitive visual pigments in insects have paralogous origins. Polymorphic amino acid sites (180, 197, 277, 285, 308), which are essential for generating the spectral diversity among the vertebrate red- and green-sensitive pigments are notably invariant in the Papilio red- and green-sensitive pigments. Other major tuning sites must be sought to explain the spectral diversification among these and other insect visual pigments.

Chromosomal position effects reveal different cis-acting requirements for rDNA transcription and sex chromosome pairing in Drosophila melanogaster.

In Drosophila melanogaster, the rDNA loci function in ribosome biogenesis and nucleolar formation and also as sex chromosome pairing sites in male meiosis. These activities are not dependent on the heterochromatic location of the rDNA, because euchromatic transgenes are competent to form nucleoli and restore pairing to rDNA-deficient X chromosomes. These transgene studies, however, do not address requirements for the function of the endogenous rDNA loci within the heterochromatin. Here we describe two chromosome rearrangements that disrupt rDNA functions. Both rearrangements are translocations that cause an extreme bobbed visible phenotype and XY nondisjunction and meiotic drive in males. However, neither rearrangement interacts with a specific Y chromosome, Ymal(+), that induces male sterility in combination with rDNA deletions. Molecular studies show that the translocations are not associated with gross rearrangements of the rDNA repeat arrays. Rather, suppression of the bobbed phenotypes by Y heterochromatin suggests that decreased rDNA function is caused by a chromosomal position effect. While both translocations affect rDNA transcription, only one disrupts meiotic XY pairing, indicating that there are different cis-acting requirements for rDNA transcription and rDNA-mediated meiotic pairing.

Evolution of color vision.

Color vision is achieved by comparing the inputs from retinal photoreceptor neurons that differ in their wavelength sensitivity. Recent studies have elucidated the distribution and phylogeny of opsins, the family of light-sensitive molecules involved in this process. Interesting new findings suggest that animals have evolved a strategy to achieve specific sensitivity through the mutually exclusive expression of different opsin genes in photoreceptors.

Intron splice sites of Papilio glaucus PglRh3 corroborate insect opsin phylogeny.

Full-length cDNA clones encoding the PglRh3 opsin from the tiger swallowtail butterfly Papilio glaucus were isolated from cDNA synthesized from adult head tissue total RNA. This cDNA consists of 1679 nucleotides and contains a single open reading frame predicted to be 379 amino acids in length. PCR amplification of genomic DNA with primers spanning the coding region yielded a single 2760bp fragment which was sequenced. The PglRh3 gene has nine exons and eight introns, four of which are in unique locations relative to the positions of introns in other known insect opsin sequences. Phylogenetic analyses of amino acid and nucleotide sequence data places PglRh3 within a clade of insect visual pigments thought to be sensitive to long wavelengths of light. The genomic structure of PglRh3 is the first characterized from a member of this opsin clade. Three PglRh3 intron positions are shared with Drosophila Rh1, and one of these is also shared with Drosophila Rh2. By contrast, none of the known intron locations in a clade of anciently diverged ultraviolet- and blue-sensitive visual pigments are shared by P. glaucus PglRh3, Drosophila Rh1 or Rh2. The placement of introns within opsin genes therefore independently supports the clustering of a putatively long-wavelength-sensitive clade with a clade of blue-green-sensitive visual pigments.

Care of the elective intracoronary stent patient.

Recently, the Palmaz-Schatz coronary stent was approved by the FDA as an alternative to coronary angioplasty in the treatment of de novo native coronary stenosis. Developed by Dr. Julio Palmaz and Dr. Richard Schatz, the Palmaz-Schatz intracoronary stent design was implanted in 1987 at Brooke Army Medical Center. During the past 7 years, The University of Texas Health Science Center-San Antonio (clinical sites include University Hospital, Brooke Army Medical Center, and Audie Murphy Veterans Administration Hospital) has used this intracoronary stent to treat more than 300 patients. Nursing care for this patient population is both distinct and challenging. Successful patient outcomes require a knowledgeable staff and a team approach. This article will emphasize the nursing care and patient education required both before and after the stent procedure, as well as considerations for long-term follow-up.

A prospective study of urine and serum myoglobin levels in patients with acute rhabdomyolysis.

Serum and urine myoglobin levels, measured by radioimmunoassay, were determined prospectively in eight patients with acute rhabdomyolysis, within 24 hours of admission. Five patients had urine myoglobin concentrations greater than 1,000 ng/ml (normal < 5 ng/ml); four of these patients subsequently developed acute renal failure. In three patients whose urinary myoglobin levels ranged from 19 to 275 ng/ml, acute renal failure did not occur. This difference in the occurrence of acute renal failure between the two patient groups was statistically significant (p < 0.05). Mean peak serum creatinine was significantly higher in the patients with high urine myoglobin (6.4 +/- 1.3 mg/dl) compared to those with low urine myoglobin (2.2 +/- 0.3 mg/dl), p < 0.02. There was no statistical correlation between level of serum creatine phosphokinase and serum or urine myoglobin, although the serum and urine myoglobin levels correlated well with each other. These findings suggests that among other factors, urine myoglobin may need to reach a critical level in order for myoglobinuric renal failure to ensue.

Serum myoglobin in patients on intermittent and continuous ambulatory peritoneal dialysis.

Serum myoglobin levels were determined in patients maintained on chronic peritoneal dialysis. Eleven intermittent peritoneal dialysis patients had a mean serum myoglobin of 174 +/- 29 ng/ml. In 7 patients tested serially, there was no consistent change in serum myoglobin: the mean level was 154 +/- 36 ng/ml pre-dialysis and 170 +/- 20 ng/ml post-dialysis. Seventeen patients on continuous ambulatory peritoneal dialysis had a mean serum myoglobin of 215 +/- 18 ng/ml. Two patients given oral carnitine supplements had a substantial decrease in their serum myoglobin levels. Patients on peritoneal dialysis, like those on hemodialysis, tend to have elevated serum myoglobin levels, and neither form of dialysis affects serum myoglobin concentration. This hypermyoglobinemia may be due to metabolic changes in muscle.